Objective To identify the hemodynamic characteristics of frontal polar cortex(FPC)in patients with chronic subjective tinnitus,and to study the short-term efficacy of multielement integration sound(MIS)treatment,and its effects on FPC oxyhemoglobin(HbO).Methods Fifty patients with chronic subjective tinnitus(tinnitus group)and 50 subjects without tinnitus matching their age,sex and education level(control group)were collected from June 2023 to Oc-tober 2023.The tinnitus group and control group received MIS treatment for 15 minutes,respectively.Tinnitus handicap inventory(THI)and visual analogue scale(VAS)scores were collected before and after treatment in tinnitus group.Func-tional near infrared spectroscopy(fNIRS)was used to measure the 8-minute average HbO concentration in the frontal cortex of both groups before and after treatment.The changes of HbO concentration before and after treatment were compared be-tween the two groups.The correlation between clinical features and HbO was analyzed.Results The VAS score of the tin-nitus group decreased after short-term MIS treatment.The HbO concentration of FPC in tinnitus group was higher than that in control group before treatment.The HbO concentration of FPC in tinnitus group was decreased by MIS short-term treatment.The difference of HbO concentration before and after treatment(ΔHbO)was positively correlated with the difference of VAS score before and after treatment(ΔVAS)in the tinnitus group.Conclusion The hemodynamics of the frontal polar cortex in chronic subjective tinnitus patients is different from that of in non-tinnitus control group.MIS can change the hemodynamics of the frontal polar cortex in chronic subjective tinnitus patients.The frontal polar cortex may be the site of MIS.

Objective:To evaluate the clinical equivalence between a domestic calcipotriol/betamethasone dipropionate ointment and the originator product in the treatment of stable plaque psoriasis.Methods:A multicenter, randomized, double-blind, three-arm, parallel-group, active- and placebo-controlled study was conducted, and 449 patients aged 18 - 65 years with stable plaque psoriasis were enrolled from 25 hospitals (such as the First Affiliated Hospital of China Medical University). Eligible patients had a baseline physician's global assessment (PGA) score of ≥ 3 points, baseline body surface area (BSA) involvement of 5% - 30%, and a target lesion psoriasis area and severity index (TL-PASI) for plaque elevation of ≥ 3 points. Participants were randomly assigned in a 2:2:1 ratio to the test group ( n = 179), reference group ( n = 180), and placebo group ( n = 90), and applied the domestic calcipotriol/betamethasone dipropionate ointment, originator product, and ointment base respectively, once daily in the evening for 4 weeks. Efficacy and safety were assessed at weeks 1, 2, and 4. The primary efficacy endpoints were the treatment success rates and clinical success rates in each group at week 4. The per-protocol set (PPS) was used for the primary efficacy analysis, and the intention-to-treat (ITT) set for supplementary efficacy analysis. Equivalence between the test and reference preparations was tested using the Cochran-Mantel-Haenszel method adjusted for randomization strata. Superiority of the test and reference preparations over the placebo was also tested. Measurement data were compared among the 3 groups using analysis of variance or non-parametric tests, while treatment success rates, clinical success rates, and incidence rates of adverse reactions were compared using the chi-square test. Results:The ITT, PPS, and safety sets included 447, 420, and 448 patients, respectively. In the ITT set, patients were aged 43.6 ± 12.8 years, including 320 (71.6%) males and 127 (28.4%) females, and the disease duration was 11.21 ± 9.05 years; 316 (70.7%) had a PGA score of 3 points and 131 (29.3%) had a PGA score of 4 - 5 points. No significant differences in the baseline characteristics (including age, sex, disease duration and disease severity) were observed among the 3 groups (all P > 0.05). Based on the PPS analysis, the treatment success rates were 57.9% (99/171) in the test group, 50.3% (86/171) in the reference group, and 7.7% (6/78) in the placebo group, and the clinical success rates were 57.9% (99/171), 50.3% (86/171), and 10.3% (8/78), respectively; both the test and reference groups were superior to the placebo group in both treatment and clinical success rates (all P < 0.001) ; the rate differences for treatment success (90% confidence interval [ CI]: -1.3% - 16.4%) and clinical success (90% CI: -1.3% - 16.3%) between the test and reference groups were entirely within the pre-defined equivalence margin (-20% - 20%). Subgroup analyses by baseline PGA scores: for patients with a baseline PGA score of 3 points, the treatment success rates in the test, reference, and placebo groups were 60.8% (73/120), 52.1% (62/119), and 11.1% (6/54), respectively, and the corresponding clinical success rates were 61.7% (74/120), 53.8% (64/119), and 13% (7/54), respectively; the test and reference groups did not differ significantly in treatment or clinical success rates (both P > 0.05), but both showed higher success rates than the placebo group (all P < 0.001) ; the results of statistical comparisons among the 3 groups in patients with a baseline PGA score of 4 - 5 points were consistent with those observed in patients with a baseline PGA score of 3 points. The percentage reductions in PGA and TL-PASI scores from baseline to weeks 1, 2, and 4 showed significant differences among the 3 groups, which were significantly higher in the test and reference groups than in the placebo group (all P < 0.001), but did not differ between the test and reference groups (all P > 0.05). The primary adverse reactions were local skin reactions, such as pruritus, pain, and erythema. The incidence rates of adverse reactions were 8.9% (16/179) in the test group, 7.3% (13/179) in the reference group, and 7.8% (7/90) in the placebo group, with no significant difference among the 3 groups ( P > 0.05) . Conclusions:The domestic calcipotriol/betamethasone dipropionate ointment demonstrated clinical equivalence to the originator product in the treatment of stable plaque psoriasis, and the two agents exhibited comparable efficacy for patients with varying degrees of disease severity, and were comparable in the speed and degree of clinical improvement, with similar favorable safety profiles.

Objective:To investigate the sleep characteristics and clinical features of patients with vestibular migraine（VM）, and to explore the influencing factors of sleep disorder in VM patients. Methods:A cross-sectional study method was adopted to collect VM patients from Otolaryngology department and neurology department of our hospital from June 2022 to June 2024（divided into sleep disorder group and non-sleep disorder group according to whether there is sleep disorder） as the experimental group, and recruit non-VM volunteers with clinical characteristics matching with the experimental group during the same period as the control group. The clinical data of the subjects were collected, and the sleep quality of the subjects was assessed using the Pittsburgh Sleep Quality Index（PSQI）. The influencing factors of sleep disorders in VM patients were analyzed by multivariate Logistic regression, and the correlation between sleep disorders and clinical features such as headache, vertigo and hearing in VM patients was analyzed by Spearman correlation coefficient. Results:A total of 530 individuals with VM were analyzed, including 332 with sleep disturbances（62.64%）, 198 without sleep issues（37.36%）, and 50 in the control group. The overall PSQI score and all its components were significantly higher in the VM group compared with the control group（P<0.05）. A positive correlation was observed between PSQI and VAS, DHI-T, DHI-E, DHI-F and DHI-P（r=0.797, P<0.05; r=0.834, P<0.05; r=0.794, P<0.05; r=0.771, P<0.05; r=0.877, P<0.05）, PSQI had no correlation with pure tone hearing（r=0.324, P=0.167）. Multivariate logistic regression analysis showed that female, age ≥60 years, living alone, duration of disease ≥3 months, motion sickness history, and HADS-A were independent influencing factors for comorbidification of sleep disorder in VM patients（P<0.05）. Conclusion:The prevalence of sleep disorders in patients with vestibular migraine（VM） was significantly higher compared to the control group. Moreover, the severity of sleep disorders was positively correlated with the intensity of headache and vertigo in VM patients. It is recommended that female VM patients aged 60 years or older, living alone, with a disease duration of three months or longer, a history of motion sickness, and anxiety symptoms undergo sleep assessments to determine the presence of sleep disorders. This approach provides a theoretical foundation for precise treatment and prevention strategies for VM.
Humans ; Migraine Disorders/complications* ; Sleep Wake Disorders/complications* ; Cross-Sectional Studies ; Vertigo ; Female ; Male ; Vestibular Diseases/complications* ; Sleep Quality ; Adult ; Middle Aged ; Logistic Models

Objective To investigate the influencing factors of auditory hypersensitivity in normal hearing population and build a risk nomogram model according to the results,so as to provide scientific basis for early identi-fication of high risk population and formulation of prevention strategy.Methods A total of 410 volunteers with nor-mal pure tone hearing were recruited from March to July 2024.The hyperacusis questionnaire(HQ)was used to as-sess the audiroty hypersensitivity of the subjects.The participants were divided into a training set(n=287)and a validation set(n=123)according to a ratio of 7∶3.Binary Logistic model was used to construct risk model and no-mogram.Receiver operating characteristic(ROC)curve,Hosmer-Lemeshow calibration curve,clinical decision curve(DCA)and clinical impact curve were used to verify the differentiation,accuracy and clinical applicability of the model,respectively.Results Among 410 participants,54(13.17％)had hyperacusis including 38(13.24％)in the training set amd 16(13.01)in the validation set.LASSO regression and Logistic regression analysis showed that tinnitus(OR=3.784,95％CI=1.627-8.804),HADS-A(OR=3.860,95％CI=1.503-9.913),HADS-D(OR=3.118,95％CI=1.249-7.785),migraine(OR=2.821,95％CI=1.147-6.937)and noise exposure histo-ry(OR=3.799,95％CI=1.715-8.416)were the influential factors for hyperacusis in participants with normal hearing.Conclusion The incidence of hyperacusis in normal hearing population is 13.17％.Tinnitus,HADS-A,HADS-D,migraine and noise exposure history are related to the occurrence of hyperacusis in normal hearing popula-tion.The risk prediction nomogram model based on the above factors has good differentiation and calibration degree.It can effectively predict the risk of hyperacusis in normal hearing people,and has certain clinical practicability.

Objective To identify the hemodynamic characteristics of frontal polar cortex(FPC)in patients with chronic subjective tinnitus,and to study the short-term efficacy of multielement integration sound(MIS)treatment,and its effects on FPC oxyhemoglobin(HbO).Methods Fifty patients with chronic subjective tinnitus(tinnitus group)and 50 subjects without tinnitus matching their age,sex and education level(control group)were collected from June 2023 to Oc-tober 2023.The tinnitus group and control group received MIS treatment for 15 minutes,respectively.Tinnitus handicap inventory(THI)and visual analogue scale(VAS)scores were collected before and after treatment in tinnitus group.Func-tional near infrared spectroscopy(fNIRS)was used to measure the 8-minute average HbO concentration in the frontal cortex of both groups before and after treatment.The changes of HbO concentration before and after treatment were compared be-tween the two groups.The correlation between clinical features and HbO was analyzed.Results The VAS score of the tin-nitus group decreased after short-term MIS treatment.The HbO concentration of FPC in tinnitus group was higher than that in control group before treatment.The HbO concentration of FPC in tinnitus group was decreased by MIS short-term treatment.The difference of HbO concentration before and after treatment(ΔHbO)was positively correlated with the difference of VAS score before and after treatment(ΔVAS)in the tinnitus group.Conclusion The hemodynamics of the frontal polar cortex in chronic subjective tinnitus patients is different from that of in non-tinnitus control group.MIS can change the hemodynamics of the frontal polar cortex in chronic subjective tinnitus patients.The frontal polar cortex may be the site of MIS.

Objective:To evaluate the clinical equivalence between a domestic calcipotriol/betamethasone dipropionate ointment and the originator product in the treatment of stable plaque psoriasis.Methods:A multicenter, randomized, double-blind, three-arm, parallel-group, active- and placebo-controlled study was conducted, and 449 patients aged 18 - 65 years with stable plaque psoriasis were enrolled from 25 hospitals (such as the First Affiliated Hospital of China Medical University). Eligible patients had a baseline physician's global assessment (PGA) score of ≥ 3 points, baseline body surface area (BSA) involvement of 5% - 30%, and a target lesion psoriasis area and severity index (TL-PASI) for plaque elevation of ≥ 3 points. Participants were randomly assigned in a 2:2:1 ratio to the test group ( n = 179), reference group ( n = 180), and placebo group ( n = 90), and applied the domestic calcipotriol/betamethasone dipropionate ointment, originator product, and ointment base respectively, once daily in the evening for 4 weeks. Efficacy and safety were assessed at weeks 1, 2, and 4. The primary efficacy endpoints were the treatment success rates and clinical success rates in each group at week 4. The per-protocol set (PPS) was used for the primary efficacy analysis, and the intention-to-treat (ITT) set for supplementary efficacy analysis. Equivalence between the test and reference preparations was tested using the Cochran-Mantel-Haenszel method adjusted for randomization strata. Superiority of the test and reference preparations over the placebo was also tested. Measurement data were compared among the 3 groups using analysis of variance or non-parametric tests, while treatment success rates, clinical success rates, and incidence rates of adverse reactions were compared using the chi-square test. Results:The ITT, PPS, and safety sets included 447, 420, and 448 patients, respectively. In the ITT set, patients were aged 43.6 ± 12.8 years, including 320 (71.6%) males and 127 (28.4%) females, and the disease duration was 11.21 ± 9.05 years; 316 (70.7%) had a PGA score of 3 points and 131 (29.3%) had a PGA score of 4 - 5 points. No significant differences in the baseline characteristics (including age, sex, disease duration and disease severity) were observed among the 3 groups (all P > 0.05). Based on the PPS analysis, the treatment success rates were 57.9% (99/171) in the test group, 50.3% (86/171) in the reference group, and 7.7% (6/78) in the placebo group, and the clinical success rates were 57.9% (99/171), 50.3% (86/171), and 10.3% (8/78), respectively; both the test and reference groups were superior to the placebo group in both treatment and clinical success rates (all P < 0.001) ; the rate differences for treatment success (90% confidence interval [ CI]: -1.3% - 16.4%) and clinical success (90% CI: -1.3% - 16.3%) between the test and reference groups were entirely within the pre-defined equivalence margin (-20% - 20%). Subgroup analyses by baseline PGA scores: for patients with a baseline PGA score of 3 points, the treatment success rates in the test, reference, and placebo groups were 60.8% (73/120), 52.1% (62/119), and 11.1% (6/54), respectively, and the corresponding clinical success rates were 61.7% (74/120), 53.8% (64/119), and 13% (7/54), respectively; the test and reference groups did not differ significantly in treatment or clinical success rates (both P > 0.05), but both showed higher success rates than the placebo group (all P < 0.001) ; the results of statistical comparisons among the 3 groups in patients with a baseline PGA score of 4 - 5 points were consistent with those observed in patients with a baseline PGA score of 3 points. The percentage reductions in PGA and TL-PASI scores from baseline to weeks 1, 2, and 4 showed significant differences among the 3 groups, which were significantly higher in the test and reference groups than in the placebo group (all P < 0.001), but did not differ between the test and reference groups (all P > 0.05). The primary adverse reactions were local skin reactions, such as pruritus, pain, and erythema. The incidence rates of adverse reactions were 8.9% (16/179) in the test group, 7.3% (13/179) in the reference group, and 7.8% (7/90) in the placebo group, with no significant difference among the 3 groups ( P > 0.05) . Conclusions:The domestic calcipotriol/betamethasone dipropionate ointment demonstrated clinical equivalence to the originator product in the treatment of stable plaque psoriasis, and the two agents exhibited comparable efficacy for patients with varying degrees of disease severity, and were comparable in the speed and degree of clinical improvement, with similar favorable safety profiles.

Objective To investigate the influencing factors of auditory hypersensitivity in normal hearing population and build a risk nomogram model according to the results,so as to provide scientific basis for early identi-fication of high risk population and formulation of prevention strategy.Methods A total of 410 volunteers with nor-mal pure tone hearing were recruited from March to July 2024.The hyperacusis questionnaire(HQ)was used to as-sess the audiroty hypersensitivity of the subjects.The participants were divided into a training set(n=287)and a validation set(n=123)according to a ratio of 7∶3.Binary Logistic model was used to construct risk model and no-mogram.Receiver operating characteristic(ROC)curve,Hosmer-Lemeshow calibration curve,clinical decision curve(DCA)and clinical impact curve were used to verify the differentiation,accuracy and clinical applicability of the model,respectively.Results Among 410 participants,54(13.17％)had hyperacusis including 38(13.24％)in the training set amd 16(13.01)in the validation set.LASSO regression and Logistic regression analysis showed that tinnitus(OR=3.784,95％CI=1.627-8.804),HADS-A(OR=3.860,95％CI=1.503-9.913),HADS-D(OR=3.118,95％CI=1.249-7.785),migraine(OR=2.821,95％CI=1.147-6.937)and noise exposure histo-ry(OR=3.799,95％CI=1.715-8.416)were the influential factors for hyperacusis in participants with normal hearing.Conclusion The incidence of hyperacusis in normal hearing population is 13.17％.Tinnitus,HADS-A,HADS-D,migraine and noise exposure history are related to the occurrence of hyperacusis in normal hearing popula-tion.The risk prediction nomogram model based on the above factors has good differentiation and calibration degree.It can effectively predict the risk of hyperacusis in normal hearing people,and has certain clinical practicability.

OBJECTIVE：To prepare Imperatorin ultradeformable liposomes gel （IMP-UDLs-Gel），and to evaluate its quality. METHODS：Based on single factor test ，using 12 h accumulative penetration amount （Q12h）as evaluation index ，the proportion of carbomer 940，glycerol and propyl glycol in formulation of IMP-UDLs-Gel were investigated by orthogonal test. The optimal formulation was screened. The quality of IMP-UDLs-Gel prepared with the optimal formulation was evaluated. RESULTS ：The optimal formulation of IMP-UDLs-Gel included carbomer 940 proportion of 1％，glycerol proportion of 15％ and propyl glycol proportion of 10％. Q12 h of IMP-UDLs-Gel was （11.543±0.241）μg/cm2；the appearance was milky white and translucent ；the particle size was （93.13±1.68）nm，PDI was 0.268±0.012，Zeta potential was （－24.96±1.99）mV；pH was 7.32±0.03； viscosity was （45.37±1.27）g·s；steady flow was （0.727±0.002）μg·h/cm2，lag time was （4.358±0.175）h，apparent permeability coefficient was 1.392×10－3 cm/h，and it has good physical and optical stability. CONCLUSIONS ：The preparation method is stable and feasible ，and the prepared IMP-UDLs-Gel has good adhesion ，stability and transdermal property.

Epigenetic modification is closely related to the occurrence and development of tumors. It mainly regulates gene function and expression level through DNA methylation, histone modification, regulation of non-coding RNA and chromatin structure reconstruction. At present, epigenetic drugs have been gradually applied to the treatment of malignant tumors. Common drug types include: DNA methyltransferase inhibitors and histone deacetylase inhibitors. However, these drugs still have many shortcomings and a wide range of clinical applications need further research. Encouragingly, the epigenetic drugs in combination with various anti-tumor drugs have shown great application potential. In this paper, we summarized the development mechanism of epigenetics in malignant tumors and the progress of related drugs.

BACKGROUND: The incidence and mortality of lung cancer often rank first in all malignant tumors. DNA methylation, as one of epigenetics, often participates in the development and progression of tumors. CDO1 as a tumor suppressor gene always undergoes methylation changes early in tumor development. Therefore, this study aims to discuss the value of CDO1 methylation in the early diagnosis of lung cancer. METHODS: Peripheral blood samples were collected from tumor patients and healthy people. Detection of the methylation level of CDO1 in plasma by sulfite modification and quantitative real-time PCR. RESULTS: The level of gene methylation in peripheral blood of lung cancer patients was significantly higher than that of benign lung disease patients and healthy people. The methylation level of CDO1 was significantly different in the stratified comparison of gender, lymph node metastasis and tumor-node-metastasis (TNM) stage (P<0.05). The sensitivity and specificity of CDO1 were 52.2% and 78.6%, respectively. The overall accuracy of the diagnosis was significantly higher than that of the clinical tumor markers, and the sensitivity of CDO1 to stage I and II patients was the highest (40.8%, 47.1%). In addition, CDO1 could effectively increase the sensitivity of diagnosis in multiple joint examinations. CONCLUSIONS Detecting the methylation level of CDO1 has a potentially huge advantage for the early diagnosis of lung cancer.